Case Report: Transjugular liver biopsy-confirmed lymphoma presenting as hemophagocytic lymphohistiocytosis with severe thrombocytopenia: a case series of three patients.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that can obscure underlying malignancies, particularly aggressive B-cell lymphoma. Severe cytopenias and coagulopathy often preclude conventional biopsy, delaying diagnosis. Objectives: To assess the diagnostic utility of transjugular liver biopsy (TJLB) in adult patients presenting with HLH, transfusion-refractory thrombocytopenia, and predominant hepatic involvement, and to explore mechanisms of thrombocytopenia. Methods: Three adult patients with HLH, hepatic lesions, and severe thrombocytopenia unresponsive to platelet transfusions were retrospectively analyzed. Conventional biopsy was contraindicated due to bleeding risk. TJLB was performed for histopathological confirmation, followed by lymphoma-directed therapy. Laboratory, imaging, and histopathological data were reviewed. Results: TJLB established aggressive B-cell lymphoma in all patients, enabling timely chemophagocytic therapy. Platelet counts normalized within 2-4 weeks (case 1 and 2), and HLH-related hyperinflammation resolved. Thrombocytopenia was multifactorial, reflecting hemophagocytosis, immune-mediated platelet destruction, hepatic sequestration, and cytokine-mediated suppression of megakaryopoiesis. Conclusions: HLH may be the first manifestation of occult lymphoma. TJLB is a safe, effective diagnostic strategy in patients with hepatic involvement and high bleeding risk, facilitating early curative therapy. These cases highlight the value of a multidisciplinary, risk-adapted diagnostic approach and provide mechanistic insight into cytopenia in HLH-associated lymphoma.